The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
最新号
December
選択された号の論文の10件中1~10を表示しています
Invited Review
  • Fatemeh Sadat Rahimi, Siamak Afaghi, Farzad Esmaeili Tarki, Kasra Moei ...
    原稿種別: Invited Review
    2022 年 258 巻 4 号 p. 243-255
    発行日: 2022年
    公開日: 2022/11/19
    [早期公開] 公開日: 2022/10/06
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    Human Monkeypox (HMPX) outbreak in the year 2022 occurs in many countries outside of the African regions, a common location of such outbreaks, with a considerable rate of human-to-human transmission, which was an uncommon route of infection before. The epidemiological reports also represent a sharping pace of infection spreading between communities rather than in previous outbreaks as the following pace of afflictions is unpredictable. Also, the cautions regarding the sexually transmitted infection of the such virus have been raised in this outbreak. Further, the main reservoirs of the recent outbreaks are yet to be revealed. As a consequence, the World Health Organization (WHO) has declared the 2022 HMPX outbreak as an “Atypical” phenomenon compared to its previous characteristics. To better recognize the properties of this outbreak, herein we systematically described and compared the historical evidence of monkeypox virus outbreaks in the aspects of epidemiological, clinical, and molecular evolutions since its emergence, as well as an explanation of the previous investigations and considerations of WHO and other international health societies over time. The history of human and monkeypox virus interaction during the past 64 years provides viewpoints on preventing strategies and assessing the present and potential future hazards of health implications.

Regular Contribution
  • Ling Li, Shasha Zhang, Junyan Liu, Yao Luo
    原稿種別: Regular Contribution
    2022 年 258 巻 4 号 p. 257-263
    発行日: 2022年
    公開日: 2022/11/11
    [早期公開] 公開日: 2022/08/11
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    Long non-coding RNA (lncRNA) is of great significance in diagnosing and prognosis of human diseases. This study aims to explore the expression of lncRNA SNHG7 in infants with neonatal sepsis and further evaluate the diagnostic and prognostic value of SNHG7 in neonatal sepsis. The expression levels of serum SNHG7 in 81 neonates were detected by quantitative real-time-PCR (qRT-PCR). The correlations between SNHG7 and clinicopathological indicators were estimated by the Pearson correlation coefficient. The receiver operating characteristic (ROC) curve was generated to assess the diagnostic value of SNHG7. Kaplan-Meier survival curve and multivariate Cox regression analysis were conducted to evaluate the prognostic value of SNHG7 in neonatal sepsis. The expression level of serum SNHG7 was significantly upregulated in the neonatal sepsis group compared to the controls, and overexpressed SNHG7 showed clinical diagnostic value for neonatal sepsis. It was observed that the SNHG7 levels were positively correlated with some indicators representing the degree of inflammation. Follow-up analysis and multivariate Cox regression revealed that the death probability of neonates with high SNHG7 level was higher than that with low SNHG7 levels, and SNHG7 was an independent factor of poor prognosis in neonates with neonatal sepsis. Together, our findings show that highly expressed SNHG7 has the potential to be a diagnostic biomarker for neonates with neonatal sepsis and was closely related to the poor prognosis of neonatal sepsis.

  • Lin Zhou, Qing Zhang, Haibin Deng, Shuobo Ou, Ting Liang, Jianlin Zhou
    原稿種別: Regular Contribution
    2022 年 258 巻 4 号 p. 265-276
    発行日: 2022年
    公開日: 2022/11/11
    [早期公開] 公開日: 2022/10/14
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    電子付録

    Hepatocellular carcinoma (HCC) is one of the most common and lethal types of cancer. This study aimed to identify the expression regulatory network and a prognostic signature of HCC. RNA-seq data from The Cancer Genome Atlas were used to identify the differentially expressed genes (DEGs) between HCC and normal liver tissues. DEGs were subjected to the construction of protein-protein interaction (PPI) network and enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The results showed that most of the DEGs were enriched in the cell cycle pathway, and the top 10 hub genes in the PPI network belong to the cell cycle pathway. A ceRNA network was constructed using starBase database, including one lncRNA (SNHG1), seven miRNAs (miR-195-5p, miR-199a-3p, miR-199a-5p, miR-199b-3p, miR-383-5p, miR-424-5p and miR-654-3p) and six of the top 10 hub genes (BUB1, CCNA2, CCNB1, KIF11, NCAPG, and TOP2A). In vitro experiments showed that knockdown of SNHG1 in the HCC cell lines (Huh7 and HepG2) decreased the expression of the six hub genes and cell viability, leading to cell cycle arrest at the G1 phase. These findings indicate that SNHG1 promotes cell proliferation by regulating cell cycle-related genes as a ceRNA. Additionally, Kaplan-Meier’s survival and multivariate Cox regression analysis identified a prognostic signature of seven genes (including SNHG1 and the six SNHG1-regulated hub genes) for overall survival of HCC patients. In conclusion, this study identified a novel regulatory network in HCC and a potential independent prognostic factor for overall survival of HCC patients.

  • Kosuke Sato, Jun Inoue, Takehiro Akahane, Tomoo Kobayashi, Satoshi Tak ...
    原稿種別: Regular Contribution
    2022 年 258 巻 4 号 p. 277-285
    発行日: 2022年
    公開日: 2022/11/12
    [早期公開] 公開日: 2022/10/14
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    Nucleos(t)ide analogues (NAs) suppress hepatitis B virus (HBV) replication, but the risk of hepatocellular carcinoma still remains. The presence of detectable HBV DNA in the serum during NA therapies for chronic hepatitis B patients has been reported to be associated with the risk of hepatocellular carcinoma. In this study, we investigated the antiviral effect of switching from entecavir (ETV) to tenofovir alafenamide fumarate (TAF) in chronic hepatitis B patients who had detectable HBV DNA in the serum at least once within a year. Among a total of 77 cases in 7 hospitals that switched NAs from ETV to TAF, 23 patients with detectable HBV DNA in a year before switching were analyzed. When the detection frequencies of HBV DNA in the 1st and 2nd years after switching to TAF were analyzed, they were significantly lower than those in the year before switching (68.8% vs. 34.1% for the 1st year and 21.3% for the 2nd year, P < 0.001 for both). The HBsAg decline tended to be larger after switching than before (−2.5% vs. −3.0% for 1st year and −3.1% for 2nd year), but the difference was not significant. One patient died of a cardiovascular event 11 months after the treatment switch, but no adverse effects due to TAF including renal function were observed. In conclusion, it was suggested that switching from ETV to TAF might be effective to suppress the HBV DNA level further in patients whose HBV DNA is detectable, even if at a very low level.

Case
  • Tetsuya Horita, Naoki Kosaka, Shinya Takaoka, Gento Fujii, Kana Fujimo ...
    原稿種別: Case
    2022 年 258 巻 4 号 p. 287-301
    発行日: 2022年
    公開日: 2022/11/12
    [早期公開] 公開日: 2022/10/20
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    We report three cases of Waterhouse-Friderichsen syndrome (WFS) that were confirmed during forensic autopsies. Case 1 involved a man in his 50s post-splenectomy. Bacteriological examination revealed Streptococcus pneumoniae (S. pneumonia). The patient was considered to have died of asphyxiation after aspirating vomit. Case 2 involved a man in his 40s. Bacteriological examination again revealed S. pneumoniae. Histopathological examination showed hypoplasia of the spleen. This patient was considered to have died of multiple-organ failure due to sepsis, disseminated intravascular coagulation, and WFS. Case 3 involved a post-splenectomy woman in her 60s with a history of systemic lupus erythematosus. Bacteriological examination revealed Streptococcus oralis. This patient was considered to have died of multiple-organ failure due to sepsis, disseminated intravascular coagulation, and WFS. These three cases were included among forensic autopsies conducted in the last 5 years. WFS has been considered a rare disease, but may be more frequent than previously assumed. If a mildly ill patient displays a sudden change in status and dies within a short period of time, we consider it necessary to perform not only bacteriological examinations, but also histopathological examination of the spleen during autopsy.

  • Yuji Fujita, Shotaro Matsudera, Shun Watanabe, Takeshi Yamaguchi, Kan ...
    原稿種別: Case
    2022 年 258 巻 4 号 p. 303-307
    発行日: 2022年
    公開日: 2022/11/11
    [早期公開] 公開日: 2022/10/20
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    Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections have increased worldwide in people without underlying diseases. CA-MRSA can often cause serious bacterial infections, especially skin and soft tissue infections (SSTI). Here, we describe a case of severe subcutaneous abscess due to Panton-Valentine leucocidin (PVL)-positive CA-MRSA in an infant without underlying diseases. A 4-month-old girl presented with a 4-day history of fever, with extensive redness and swelling of the lumbar region and buttocks. She was diagnosed with extensive subcutaneous abscess of the lumbar region and buttocks. Surgical drainage was performed, and a substantial volume of pus was drained. MRSA was detected in the pus on culture. Antibiotic therapy that covered MRSA was also administered for 3 weeks, and the abscess healed. As it was a severe SSTI due to MRSA, analysis of MRSA revealed PVL-positive MRSA. This patient had no underlying disease or history of antibiotic administration, and as MRSA was present in the nasopharyngeal cavity, it was considered a case of CA-MRSA. Furthermore, the prevalence of PVL-positive CA-MRSA in MRSA isolated from patients with SSTI has also increased in Japan. The Infectious Diseases Society of America recommends surgical intervention and empirical antibiotic therapy for MRSA-complicated SSTI cases in an era of CA-MRSA. Pediatricians must strongly consider the possibility of MRSA in children with severe SSTIs.

Regular Contribution
  • Yong Wang, Jianjun Luo, Sheng Hu, Qiong Guo, Xi Guo, Weigang Ren, Qian ...
    原稿種別: Regular Contribution
    2022 年 258 巻 4 号 p. 309-317
    発行日: 2022年
    公開日: 2022/11/19
    [早期公開] 公開日: 2022/09/23
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    A previous study confirmed that miRNAs play an important role in the chemosensitivity of seminoma. Increasing evidence reveals that exosomes participate in the regulation of cisplatin resistance by carrying miRNAs. In this study, we further explored whether exosomes regulated the chemosensitivity of seminoma TCam-2 cells to cisplatin. Initially, cisplatin-resistant TCam-2 cells were induced. Our results revealed that exosomes from cisplatin-resistant TCam-2 cells (rExos) could affect the viability of TCam-2 cells in the context of cisplatin treatment through regulation of both cell apoptosis and the cell cycle. Meanwhile, the levels of γ-H2AX were negatively modulated by rExos, which indicated that rExos could decrease the DNA damage from cisplatin. Furthermore, miR-193b-3p was enriched in rExos, and exosomal miR-193b-3p enhanced the proliferative ability of TCam-2 cells under cisplatin treatment. Mechanistically, exosomal miR-193b-3p targets ZBTB7A, which further decreases apoptosis and promotes cell cycle progression. Taken together, these findings indicate that exosomal miR-193b-3p regulates the chemosensitivity of TCam-2 cells to cisplatin through ZBTB7A signaling and could be a promising drug target for patients with chemoresistant seminoma.

  • Gülay Güleç Ceylan, S. Betül Arslan Satılmış, Büşranur Çavdarlı, C. Nu ...
    原稿種別: Regular Contribution
    2022 年 258 巻 4 号 p. 319-325
    発行日: 2022年
    公開日: 2022/11/22
    [早期公開] 公開日: 2022/10/27
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    Cancer is a clonal disease that develops as a result of the changes on the genetic material by various factors in micro/macro environment. It has a multi-step development process. In some cancer types, genetic factors allow this multi-step process to proceed easily. These cancer types are also called hereditary cancer syndromes. Targeted gene panels are important diagnostic methods in hereditary cancer syndromes to detect the causative variants associated with these hereditary cancer syndromes. We reviewed the data of 94 patients who applied to Ankara City Hospital Genetic Diseases Evaluation Center from March 2019 to July 2021. Qiagen familial cancer susceptibility gene panel kit was used for next generation sequencing to detect the single nucleotide variants for the targeted genes. Sixty-one genes which are associated with increased cancer risk or well characterized hereditary cancer syndromes were included to this panel. Twenty five patients (27%), including 8 males and 17 females, had pathogenic/likely pathogenic variants in 13 of the 61 genes analyzed. Forty patients (43%) had variants which were assessed as variant of unknown significant. In our study, targeted multi-gene panel was diagnostic in nearly one third of the patients with personal/familial cancer syndromes. Molecular diagnosis in familial cancer syndromes is important in terms of predictive diagnosis and family screening, as well as patient follow-up and early prophylactic surgery. The predisposition for hereditary cancer syndromes can be determined according to pre-test evaluation, figuring out the inheritance type with pedigree analysis, cancer type and the genetic analysis for appropriate susceptibility genes.

Case
  • Kohei Takikawa, Ryosuke Doijiri, Naoto Kimura, Ako Miyata, Takuji Sono ...
    原稿種別: Case
    2022 年 258 巻 4 号 p. 327-332
    発行日: 2022年
    公開日: 2022/11/23
    [早期公開] 公開日: 2022/11/10
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    Antithrombin deficiency is a high-risk factor for venous thromboembolism during pregnancy, whereas cerebral venous thrombosis is rare. Cerebral venous thrombosis related to coronavirus disease 2019 (COVID-19) vaccines has been reported; however, there are a few reports of cerebral venous thrombosis after a messenger RNA (mRNA) vaccination. A 25-year-old female in her sixth week of pregnancy presented with headache 24 days after BNT162b2 mRNA COVID-19 vaccination. The following day, she presented with altered sensorium and was diagnosed with severe cerebral venous thrombosis. She demonstrated heparin resistance and was found to have an inherited antithrombin deficiency. A heterozygous missense variant in SERPINC1 (c.379T>C, p.Cys127Arg, ‘AT Morioka’) was detected by DNA analysis. Despite intensive care with unfractionated heparin, antithrombin concentrate, and repeated endovascular treatments, she died on the sixth day of hospitalization. Cerebral venous thrombosis in pregnant women with an antithrombin deficiency can follow a rapid and fatal course. Treatment with unfractionated heparin and antithrombin concentrate may be ineffective in severe cerebral venous thrombosis cases with antithrombin deficiency. Early recognition of antithrombin deficiency and an immediate switch to other anticoagulants may be required. Although the association between cerebral venous thrombosis and the vaccine is uncertain, COVID-19 vaccinations may require careful evaluation for patients with prothrombic factors.

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